{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T13:40:41Z","timestamp":1767188441312,"version":"3.48.0"},"reference-count":26,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"},{"start":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T00:00:00Z","timestamp":1765756800000},"content-version":"vor","delay-in-days":14,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key R&D Program of China","doi-asserted-by":"crossref","award":["2023YFC2706100"],"award-info":[{"award-number":["2023YFC2706100"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100016697","name":"Youth Innovation Technology Project of Higher School in Shandong Province","doi-asserted-by":"publisher","award":["NO.tstp20230660"],"award-info":[{"award-number":["NO.tstp20230660"]}],"id":[{"id":"10.13039\/100016697","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82425054"],"award-info":[{"award-number":["82425054"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82273784"],"award-info":[{"award-number":["82273784"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Drugs R D"],"published-print":{"date-parts":[[2025,12]]},"DOI":"10.1007\/s40268-025-00528-3","type":"journal-article","created":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T18:04:24Z","timestamp":1765821864000},"page":"387-396","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pharmacokinetics, Pharmacodynamics, and Safety of ET-26 in Subjects with Mild to Moderate Renal Impairment"],"prefix":"10.1007","volume":"25","author":[{"given":"Fan","family":"Yang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chao-Zhuang","family":"Shen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pan-Pan","family":"Ye","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen-Shuo","family":"Lv","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li-Ze","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Shao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Diao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo-Wen","family":"Ke","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao-Ran","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1830-338X","authenticated-orcid":false,"given":"Wei","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,12,15]]},"reference":[{"key":"528_CR1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0183439","volume":"12","author":"B Wang","year":"2017","unstructured":"Wang B, Chen S, Yang J, Yang L, Liu J, Zhang W. ET-26 hydrochloride (ET-26 HCl) has similar hemodynamic stability to that of etomidate in normal and uncontrolled hemorrhagic shock (UHS) rats. PLoS ONE. 2017;12:e0183439.","journal-title":"PLoS ONE"},{"key":"528_CR2","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1016\/j.bja.2024.09.009","volume":"134","author":"Q Yin","year":"2025","unstructured":"Yin Q, Yang Y, Liu J, Li L, Yang X, Diao L, et al. Phase 1 single-centre placebo- and etomidate-controlled study in healthy volunteers to assess safety, tolerability, clinical effects, and pharmacokinetics of intravenous methoxyethyl etomidate hydrochloride (ET-26). Br J Anaesth. 2025;134:80\u20138.","journal-title":"Br J Anaesth"},{"key":"528_CR3","doi-asserted-by":"publisher","first-page":"1415","DOI":"10.1056\/NEJM198405313102202","volume":"310","author":"RL Wagner","year":"1984","unstructured":"Wagner RL, White PF, Kan PB, Rosenthal MH, Feldman D. Inhibition of adrenal steroidogenesis by the anesthetic etomidate. N Engl J Med. 1984;310:1415\u201321.","journal-title":"N Engl J Med"},{"key":"528_CR4","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1097\/ALN.0b013e3181ff72b5","volume":"114","author":"SA Forman","year":"2011","unstructured":"Forman SA. Clinical and molecular pharmacology of etomidate. Anesthesiology. 2011;114:695\u2013707.","journal-title":"Anesthesiology"},{"key":"528_CR5","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1007\/s00134-005-2560-1","volume":"31","author":"D Annane","year":"2005","unstructured":"Annane D. ICU physicians should abandon the use of etomidate! Intensive Care Med. 2005;31:325\u20136.","journal-title":"Intensive Care Med"},{"key":"528_CR6","doi-asserted-by":"publisher","first-page":"442","DOI":"10.1213\/ANE.0000000000002063","volume":"125","author":"B Wang","year":"2017","unstructured":"Wang B, Yang J, Chen J, Kang Y, Yang LH, Liu J, et al. An etomidate analogue with less adrenocortical suppression, stable hemodynamics, and improved behavioral recovery in rats. Anesth Analg. 2017;125:442\u201350.","journal-title":"Anesth Analg"},{"key":"528_CR7","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1016\/j.ejps.2017.09.005","volume":"109","author":"B Wang","year":"2017","unstructured":"Wang B, Jiang J, Yang J, Chen J, Zhu Z, Liu J, et al. Pharmacologic studies on ET-26 hydrochloride in a rat model of lipopolysaccharide-induced sepsis. Eur J Pharm Sci. 2017;109:441\u20135.","journal-title":"Eur J Pharm Sci"},{"key":"528_CR8","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1002\/jat.3936","volume":"40","author":"Y Zhang","year":"2020","unstructured":"Zhang Y, Deng C, Gong D, Kang Y, Liu J, Zhang W. Preclinical safety evaluation of ET-26 hydrochloride, a novel intravenous anesthetic agent, in beagle dogs. J Appl Toxicol. 2020;40:679\u201390.","journal-title":"J Appl Toxicol"},{"key":"528_CR9","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1681\/ASN.V122326","volume":"12","author":"F Leblond","year":"2001","unstructured":"Leblond F, Gu\u00e9vin C, Demers C, Pellerin I, Gascon-Barr\u00e9 M, Pichette V. Downregulation of hepatic cytochrome P450 in chronic renal failure. J Am Soc Nephrol. 2001;12:326\u201332.","journal-title":"J Am Soc Nephrol"},{"key":"528_CR10","doi-asserted-by":"publisher","first-page":"1065","DOI":"10.1517\/17425255.4.8.1065","volume":"4","author":"AW Dreisbach","year":"2008","unstructured":"Dreisbach AW, Lertora JJ. The effect of chronic renal failure on drug metabolism and transport. Expert Opin Drug Metab Toxicol. 2008;4:1065\u201374.","journal-title":"Expert Opin Drug Metab Toxicol"},{"key":"528_CR11","doi-asserted-by":"publisher","first-page":"574","DOI":"10.1053\/j.ajkd.2014.09.015","volume":"65","author":"BK Thomson","year":"2015","unstructured":"Thomson BK, Nolin TD, Velenosi TJ, Feere DA, Knauer MJ, Asher LJ, et al. Effect of CKD and dialysis modality on exposure to drugs cleared by nonrenal mechanisms. Am J Kidney Dis. 2015;65:574\u201382.","journal-title":"Am J Kidney Dis"},{"key":"528_CR12","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.pharmthera.2005.05.010","volume":"109","author":"H Sun","year":"2006","unstructured":"Sun H, Frassetto L, Benet LZ. Effects of renal failure on drug transport and metabolism. Pharmacol Ther. 2006;109:1\u201311.","journal-title":"Pharmacol Ther"},{"unstructured":"U.S. Food and Drug Administration. Pharmacokinetics in Patients with Impaired Renal Function \u2014 Study Design, Data Analysis, and Impact on Dosing: Guidance for Industry. Silver Spring (MD): U.S. Food and Drug Administration; 2024 Mar 15. Guidance. Available from FDA website.15 March 2024. https:\/\/www.fda.gov\/regulatory-information\/search-fda-guidance-documents\/pharmacokinetics-patients-impaired-renal-function-study-design-data-analysis-and-impact-dosing?utm_source=chatgpt.com.","key":"528_CR13"},{"unstructured":"European Medicines Agency (EMA). Guideline on the evaluation of the pharmacokinetics of medicinal products in patients with decreased renal function (EMA\/CHMP\/83874\/2014). https:\/\/www.ema.europa.eu\/en\/documents\/scientific-guideline\/guideline-evaluation-pharmacokinetics-medicinal-products-patients-decreased-renal-function_en.pdf.","key":"528_CR14"},{"unstructured":"National Medical Products Administration (NMPA), Centre for Drug Evaluation (CDE). Technical guideline for pharmacokinetic studies in subjects with impaired renal function. Beijing: NMPA (CDE); 2022. https:\/\/www.cde.org.cn\/main\/news\/viewInfoCommon\/c8a93c12537f5e8a624e57bbfd80f2bd.","key":"528_CR15"},{"unstructured":"National Medical Products Administration (NMPA), Centre for Drug Evaluation (CDE). Technical guidelines for clinical evaluation of intravenous general anesthetics. Beijing: NMPA (CDE); 2022. https:\/\/www.cde.org.cn\/main\/news\/viewInfoCommon\/8e75d4b87268d6e5e7e7bf03d8375ee6.","key":"528_CR16"},{"key":"528_CR17","doi-asserted-by":"publisher","DOI":"10.1007\/s13318-025-00963-2","author":"DE Murrell","year":"2025","unstructured":"Murrell DE, Harirforoosh S. Clinical pharmacokinetics, pharmacodynamics, and drug interactions of remimazolam. Eur J Drug Metab Pharmacokinet. 2025. https:\/\/doi.org\/10.1007\/s13318-025-00963-2.","journal-title":"Eur J Drug Metab Pharmacokinet"},{"key":"528_CR18","doi-asserted-by":"publisher","first-page":"456","DOI":"10.1186\/s12871-024-02845-7","volume":"24","author":"H Liu","year":"2024","unstructured":"Liu H, Luo R, Qian L, Zhang Y, Zhang W, Tan J, et al. The effect of dexmedetomidine on acute kidney injury after elective major abdominal surgery: a retrospective single-center propensity score matched study. BMC Anesthesiol. 2024;24:456.","journal-title":"BMC Anesthesiol"},{"key":"528_CR19","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0254520","volume":"16","author":"MR Jun","year":"2021","unstructured":"Jun MR, Kim MG, Han KS, Park JE, Cho HB, Park SY, et al. Potency of propofol for inducing loss of consciousness in end-stage kidney disease patients. PLoS ONE. 2021;16:e0254520.","journal-title":"PLoS ONE"},{"key":"528_CR20","doi-asserted-by":"publisher","first-page":"1401","DOI":"10.1016\/j.bja.2018.01.038","volume":"120","author":"BI Valk","year":"2018","unstructured":"Valk BI, Absalom AR, Meyer P, Meier S, den Daas I, van Amsterdam K, et al. Safety and clinical effect of i.v. infusion of cyclopropyl-methoxycarbonyl etomidate (ABP-700), a soft analogue of etomidate, in healthy subjects. Br J Anaesth. 2018;120:1401\u201311.","journal-title":"Br J Anaesth"},{"key":"528_CR21","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1097\/ALN.0000000000001662","volume":"127","author":"M Struys","year":"2017","unstructured":"Struys M, Valk BI, Eleveld DJ, Absalom AR, Meyer P, Meier S, et al. A phase 1, single-center, double-blind, placebo-controlled study in healthy subjects to assess the safety, tolerability, clinical effects, and pharmacokinetics-pharmacodynamics of intravenous cyclopropyl-methoxycarbonylmetomidate (ABP-700) after a single ascending bolus dose. Anesthesiology. 2017;127:20\u201335.","journal-title":"Anesthesiology"},{"key":"528_CR22","doi-asserted-by":"publisher","first-page":"1253","DOI":"10.1007\/s40262-021-01038-6","volume":"60","author":"BI Valk","year":"2021","unstructured":"Valk BI, Struys MMRF. Etomidate and its analogs: a review of pharmacokinetics and pharmacodynamics. Clin Pharmacokinet. 2021;60:1253\u201369.","journal-title":"Clin Pharmacokinet"},{"key":"528_CR23","doi-asserted-by":"publisher","DOI":"10.1186\/s12871-025-03099-7","volume":"25","author":"M Alipour","year":"2025","unstructured":"Alipour M, Firuzabadi SJP. Investigating the effect of ondansetron in reducing myoclonic movements caused by intravenous administration of etomidate. BMC Anesthesiol. 2025;25:224.","journal-title":"BMC Anesthesiol"},{"key":"528_CR24","doi-asserted-by":"publisher","DOI":"10.7717\/peerj.13995","volume":"10","author":"P Chang","year":"2022","unstructured":"Chang P, Su Y, Gong D, Kang Y, Liu J, Zhang Y, et al. The preclinical pharmacological study of a novel intravenous anesthetic, ET-26 hydrochloride, in aged rats. PeerJ. 2022;10:e13995.","journal-title":"PeerJ"},{"key":"528_CR25","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1186\/cc11242","volume":"16","author":"G Flynn","year":"2012","unstructured":"Flynn G, Shehabi Y. Pro\/con debate: is etomidate safe in hemodynamically unstable critically ill patients? Crit Care. 2012;16:227.","journal-title":"Crit Care"},{"key":"528_CR26","doi-asserted-by":"publisher","first-page":"901","DOI":"10.1007\/s00134-011-2160-1","volume":"37","author":"SG Albert","year":"2011","unstructured":"Albert SG, Ariyan S, Rather A. The effect of etomidate on adrenal function in critical illness: a systematic review. Intensive Care Med. 2011;37:901\u201310.","journal-title":"Intensive Care Med"}],"container-title":["Drugs in R&D"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40268-025-00528-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s40268-025-00528-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40268-025-00528-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T13:36:08Z","timestamp":1767188168000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s40268-025-00528-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12]]},"references-count":26,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["528"],"URL":"https:\/\/doi.org\/10.1007\/s40268-025-00528-3","relation":{},"ISSN":["1174-5886","1179-6901"],"issn-type":[{"type":"print","value":"1174-5886"},{"type":"electronic","value":"1179-6901"}],"subject":[],"published":{"date-parts":[[2025,12]]},"assertion":[{"value":"24 August 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 November 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 December 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This observational study adhered to the principles of the Declaration of Helsinki and Ethical Guidelines for Medical and Health Research Involving Human Subjects. The clinical study protocol and the informed consent form, as well as their amendments, had been reviewed and approved by the Ethics Committee of the Shandong Provincial Qianfoshan Hospital before implementation. This study was registered in the Center for Drug Evaluation (CDE) Clinical Trial Registry, National Medical Products Administration (NMPA), China, with the registration number CTR20233783, on November 23, 2023. Clinical Trial registration identifier: NCT05789342.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Written informed consent was obtained from all enrolled patients.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"The study patients were informed that a compilation of data would be published in a medical journal.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to publication"}},{"value":"The authors declare no competing interests.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"The data underlying this article will be shared on reasonable request to the corresponding author.","order":6,"name":"Ethics","group":{"name":"EthicsHeading","label":"Data sharing statement"}},{"value":"Fan Yang, Chao-Zhuang Shen: Data analysis, manuscript writing; Pan-Pan Ye, Wen-Shuo Lv: Clinical sample processing; Li-Ze Li, Jie Shao, Lei Diao: Study design; Wei Zhao, Xiao-Ran Yang, Yi Zheng, Bo-Wen Ke: Project administration.","order":7,"name":"Ethics","group":{"name":"EthicsHeading","label":"Author contributions"}},{"value":"The authors confirm that the Principal Investigator for this paper is Wei Zhao and that he had direct clinical responsibility for patients.","order":8,"name":"Ethics","group":{"name":"EthicsHeading","label":"Principal Investigator statement"}},{"value":"Not applicable.","order":9,"name":"Ethics","group":{"name":"EthicsHeading","label":"Code availability"}}]}}